Preform for blow molded syringe for use with injectors

ABSTRACT

A syringe for use in a pressurized injection of a fluid includes a syringe barrel including a polymeric material having undergone expansion via blow molding. A preform for blow molding a blow molded syringe is described, the preform including a proximal end having a retention mechanism adapted to connect to the syringe to a powered injector, a distal end having a syringe outlet section, and a barrel section between the retention mechanism and the syringe outlet section, wherein the barrel section is adapted to be blow molded to form a cylindrical wall of a syringe barrel defined between the retention mechanism and the syringe outlet section.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of co-pending U.S.application Ser. No. 14/605,066, filed Jan. 26, 2015, which iscontinuation application of Ser. No. 12/794,990, filed Jun. 7, 2010, nowU.S. Pat. No. 8,939,940, which is a divisional application to U.S.application Ser. No. 11/833,427, filed Aug. 3, 2007, now U.S. Pat. No.7,740,792, which claims priority to U.S. Provisional Application Ser.No. 60/821,314, filed Aug. 3, 2006, the disclosures of each of which areincorporated herein by this reference.

BACKGROUND OF THE DISCLOSURE

The present disclosure relates generally to syringes for use withinjectors and to methods of manufacturing syringes and other devicesand, particularly, to syringes manufactured by blow molding and tomethods of blow molding syringes and other devices.

In many medical procedures, such as drug delivery, it is desirable toinject a fluid into a patient. Likewise, numerous types of contrastmedia (often referred to simply as contrast) are injected into a patientfor many diagnostic and therapeutic procedures for example, genetherapy, cell and biological agent delivery, and delivery of therapeuticagents generally). For example, contrast media are used in diagnosticprocedures such as X-ray procedures (including, for example,angiography, venography, urography,), computed tomography (CT) scanning,magnetic resonance imaging (MRI), and ultrasonic imaging. Contrast mediaare also used during therapeutic procedures, including, for example,angioplasty and other interventional radiological procedures.

A number of injector-actuated syringes and powered injectors for use inmedical procedures such as angiography, computed tomography (CT),ultrasound and NMR/MRI have been developed. A front-loading syringe andinjector system is, for example, disclosed in U.S. Pat. No. 5,383,858,assigned to the assignee of the present disclosure, the disclosure ofwhich is incorporated herein by reference. Other front-loading syringesand injectors systems are, for example, disclosed in U.S. Pat. No.6,652,489, the disclosures of which are incorporated herein byreference.

Historically, it has been difficult to manufacture syringes withdesirable transparent optical properties that exhibit sufficientstrength for use with front-loading, pressure jacketless injectors.Indeed, depending upon the application, syringe pressures in the rangeof 300 psi to 1200 psi are commonly experienced in injection proceduresusing powered injectors. Typically, to achieve suitable strength, thesyringe walls must be thickened during manufacture, which increasescosts and, depending upon the material, can degrade optical properties.However, in the current injection molding practices for manufacturingsyringe, there is a limit to the wall thickness that can be achieved.This limit can result in syringes designed with a lower safety factorthan desirable. Moreover, as wall thickness is increased, productioncosts also increase. For example, increases in wall thickness areassociated with longer injection times, longer packing times, higherpressures, longer cooling time, and increased resin costs.

It is desirable to develop new syringes and methods of fabricating ormanufacturing syringes that reduce or eliminate the above-identified andother problems associated with current syringes and methods ofmanufacture.

BRIEF SUMMARY

In one aspect, the present disclosure provides a syringe for use in apressurized injection of a fluid. The syringe includes a syringe barrelincluding a polymeric material having undergone expansion via blowmolding. An inner diameter of the syringe barrel can, for example, besufficiently constant (over at least a portion of the axial length ofthe syringe) that a plunger slidably positioned within the syringebarrel and in generally sealing contact with an inner wall of thesyringe barrel can be used within the syringe barrel to generate apressure to inject a fluid contained within the syringe barrel. Thesyringes of the present disclosure can be used in both low pressure andhigh pressure application. For example, the constancy of the innerdiameter of the syringe barrels of the syringes of the presentdisclosure is suitable to generate a pressure of at least 1 psi withinthe syringe barrel or of, for example, at least 100 psi within thesyringe barrel. In several embodiments, the diameters of the inner wallsof the syringe barrels of the present disclosure are suitably constantto generate a pressure of at least 200 psi, at least 300 psi, or even atleast 500 psi within the syringe barrel.

The inner diameter of the syringe wall can, for example, vary no morethan 0.01 in. The inner diameter of the syringe can also vary by no morethan 0.007 in. or even no more than 0.004 in.

The polymeric material can, for example, undergo biaxial orientation viainjection stretch blow molding.

The syringe can, for example, include one or more portions, sections orcomponents that are molded to certain predefined acceptable tolerancesfor a predefined use. Such molded portions, sections or components aresometimes referred to herein as “precision molded” portions, sections orcomponents. For example, the syringe can include one or more attachmentmechanisms positioned, for example, to the rear of the syringe barrel.Likewise, one or more attachment mechanism and/or other precision moldedportions can be formed on or in the vicinity of the forward end of thesyringe, in the vicinity of the syringe outlet.

In several embodiments, the polymeric material of the syringe includes,for example, at least one of polyethyleneterephthalate (PET), cyclicolefin polymer, polypropylene, polystyrene, polyvinylidene chloride,polyethylene naphthalate (PEN) or nylon. The polymeric material can be acoinjected material of one or more of the above identified polymersand/or other polymers. Examples of coinjected materials include, but arenot limited to, PET/PEN or PET/nylon. The syringe can include a firstlayer of a first polymeric material and at least a second layer of asecond polymeric material, different from the first polymeric material.At least one of the first polymeric material can, for example, includepolyethyleneterephthalate, cyclic olefin polymer, polypropylene,polystyrene, polyvinylidene chloride, polyethylene naphthalate or nylon.The first and/or the second polymeric material can, for example, includea single polymer or blends of two or more polymers. As used herein, theterm “polymer” includes homopolymers which are synthesized from a singlemonomer and copolymers which are synthesized from two or more differentmonomers. The polymeric materials of the first layer and the secondlayer can, for example, differ in one or more respects such ascomposition, molecular weight, crystallinity, barrier properties etc.

The syringe barrels can, for example, withstand relatively highpressures. For example, the syringe barrel can withstand pressures of atleast 1 psi, at least 100 psi, at least 150 psi, at least 200 psi, atleast 300 psi, at least 500 psi or even at least 1200 psi.

The walls of the syringe barrel can be relatively thin. For example, thewall of the syringe barrel can be less than 0.07 inches in thickness oreven less than 0.05 inches in thickness.

The method can further include a heat setting process. For example, aheat setting process can be used to maintain a suitable dimension ofinternal diameter of a syringe barrel (or, for example, other open endedmedical devices and other devices). A heat setting process can also, forexample, be used to minimize fluid capacitance of a syringe barrel orother open ended medical device (or, for example, other open endedmedical devices and other devices).

In another aspect, the present disclosure provides a method of forming asyringe including the steps of: injection molding at least one polymericmaterial to form a preform; placing the preform into a blow mold die;and expanding at least a portion of the preform within the die to form abarrel of the syringe. Those components, elements, portions or sectionsof the preform to be blow molded/expanded (for example, the barrelportion of the syringe) are typically heated (above the glass transition(T_(g)) of the polymeric material(s)) prior to placing the preformwithin the blow mold die. During the preheating process, precisionmolded components, portions or sections of the preform can be protectedfrom heating (that is, maintained at a lower temperature) to, forexample, maintain molded dimensions within acceptable tolerances. Thoseportions or sections of the preform to be expanded within the blow molddie can also be heated during the blow molding process. The syringes canbe formed for use at low pressure or to withstand relatively highpressures as described above. The at least one polymeric material can,for example, be polyethyleneterephthalate, cyclic olefin polymer,polypropylene, polystyrene, polyvinylidene chloride, polyethylenenaphthalate or nylon. The method can further include a heat settingprocess.

Injection molding the preform can, for example, include forming one ormore portions molded to dimension of predefined acceptable tolerancesuch as an attachment mechanism (positioned, for example, adjacent aproximal or rearward end of the syringe), which is adapted to connectthe syringe to, for example, a powered injector. The attachmentmechanism can, for example, include at least one flange. The tolerancesof precision molded portions such as injector attachment mechanisms aremaintained during blow molding. For example, the attachment mechanism orother precision molded portion is not altered or substantially altered(for example, such that an attachment mechanism does not suitably retainthe syringe upon an injector) during the expansion of the preform.Injection molding the preform can also include forming a connector orother precision molded portion adjacent a distal end of the preform. Theconnector or other precision molded portion is not altered orsubstantially altered during expansion of the preform.

Expanding at least a portion of the preform can include forcing of a gaswithin the preform and axial extension of an extension rod within thepreform. Injection molding the preform can also include forming asyringe outlet section at a distal end of the preform, wherein thepreform including a passage between a barrel section thereof and thesyringe outlet section. The extension rod can, for example, form atleast a partial seal with the passage during expansion of the preform.In several embodiments, injection molding the preform can also includeforming a connector or attachment mechanism (for example, a Luerconnector) during injection molding of the preform as described above,which is positioned adjacent the distal end of the preform. Once again,the connector is not altered or substantially altered during expansionof the preform.

A removable closure can be formed on a distal end of the outlet sectionduring injection molding. The closure can, for example, be removablyconnected to the outlet section via a wall section of reduced thickness.

In another aspect, the present disclosure provides a method of forming asyringe for use with an injector including injection molding a polymericmaterial to form a removable closure integrally with an outlet sectionor opening of the syringe. The removable closure can, for example, beformed during injection molding of a preform for the syringe which issubsequently blow molded to form the syringe. As described above, theclosure can be removably connected to the outlet section via a wallsection of reduced thickness.

In a further aspect, the present disclosure provides a syringe includinga barrel, an outlet section integrally formed with the barrel at adistal end of the barrel and a removable closure integrally formed withthe outlet section at a distal end of the outlet section. The closurecan, for example, be removably connected to the outlet section via awall section of reduced thickness.

In another aspect, method of forming a syringe for use with an injector,including: forming a preform comprising a syringe outlet section on adistal end thereof and a closed section corresponding to a precursor ofa barrel section of the syringe on the proximal end thereof by injectingat least one polymeric material into a mold for the preform; placing thepreform into an blow mold die; and expanding at least a portion of thepreform by passing pressurized gas into the interior of the syringe viaan outlet opening in the outlet section to form a barrel of the syringe.As described above, those portions or sections of the preform to be blowmolded/expanded (for example, the barrel portion of the syringe) aretypically heated (above the glass transition (T_(g)) of the polymericmaterial(s)) prior to placing the preform within the blow mold die.During the preheating process, precision molded components, portions orsections of the preform can be protected from heating (that is,maintained at a lower temperature) to, for example, maintain moldeddimensions within acceptable tolerances. Once again, those portions orsections of the preform to be expanded within the blow mold die can alsobe heated during the blow molding process. The syringe can be formed towithstand low pressures and/or relatively high pressures (for example,pressures of at least 100 psi or higher) as described above. The formedsyringe can be closed on the proximal end thereof via a removableclosure formed integrally or monolithically with the syringe. Theremovable closure can, for example, form a plunger section upon removalfrom connection with the syringe.

In a further aspect, the present disclosure provides a syringe includingan outlet section on a distal end thereof. The outlet section includesan outlet opening. A barrel section is integrally or monolithicallyformed with the outlet section. A disengageable closure is integrally ormonolithically formed at a proximal end of the syringe. In severalembodiments, the closure forms at least part of a syringe plunger upondisengagement from the barrel section.

In still a further aspect, the present disclosure provides a syringeincluding a syringe wall comprising a first layer of a first polymericmaternal and at least a second layer of a second polymeric material,different from the first polymeric material. One of the first layer andthe second layer can, for example, include polyethyleneterephthalate,cyclic olefin polymer, polypropylene, polystyrene, polyvinylidenechloride, polyethylene naphthalate and/or nylon. The first layer can,for example, be radially inward from the second layer and have greaterlubricity than the second layer. One of the first layer and the secondlayer can, for example, have better barrier properties than the other ofthe first layer and the second layer.

In still a further aspect, the present disclosure provides a method offorming a device including a first opening, a second opening and a flowpath between the first opening and the second opening. The methodincludes: injection molding at least one polymeric material to form apreform, the preform including a first molded portion in the vicinity ofthe first opening that is molded to acceptable tolerances; placing thepreform into an blow mold die; and expanding an intermediate portion ofthe preform intermediate between the first opening and the secondopening within the die by blowing a gas into the preform and axiallyextending an extension rod within the preform. The extension rod abuts asection of the preform and forms at least a partially sealing closurebetween the flow path and the first opening during extension thereof.The intermediate portion of the preform is expanded while maintainingthe acceptable tolerances of the first molded portion. The method canfurther include heating the intermediate portion of the preform beforeplacing the preform into the blow mold die. The method can also includeheating the intermediate portion of the preform during expansion withinthe die. The method can further include a heat setting process.

In several embodiments, the device is a medical device adapted to form acomponent of a fluid flow system. In a number of embodiments, the deviceis a syringe.

The preform can, for example, further include a second molded portion inthe vicinity of the second opening that is molded to acceptabletolerances. The intermediate portion of the preform is expanded whilemaintaining the acceptable tolerances of the second molded portion.

The polymeric material can, for example, includepolyethyleneterephthalate, cyclic olefin polymer, polypropylene,polystyrene, polyvinylidene chloride, polyethylene naphthalate and/ornylon.

In still another aspect, the present disclosure provides a system forforming a device including a first opening, a second opening and a flowpath between the first opening and the second opening. The systemincludes a blow mold die adapted to receive an injection molded preform.The preform further includes a first molded portion in the vicinity ofthe first opening that is molded to acceptable tolerances. The blow molddie includes a forward section shaped to receive the first moldedportion. The system further includes an extension rod axially movablewithin the blow mold die to assist in axially expanding an intermediateportion of the preform intermediate between the first opening and thesecond opening within the die while gas is blown into the preform. Theextension rod is adapted to abut a section of the preform and form atleast a partially sealing closure between the flow path and the firstopening during extension thereof. In several embodiments, the blow molddie further includes a rearward section shaped to receive a secondmolded portion in the vicinity of the second opening that is molded toacceptable tolerances. Cooperation between the rearward section and thesecond molded portion can, for example, operate to retain the preform inthe blow mold die during expansion of the intermediate section. Themethod can further include a heat setting process.

BRIEF DESCRIPTION OF THE DRAWINGS

Other aspects of the disclosure and their advantages will be discernedfrom the following detailed description when read in connection with theaccompanying drawings, in which:

FIG. 1A illustrates an embodiment of a preform of the presentdisclosure.

FIG. 1B illustrates the stretch blow molding of the preform of FIG. 1Ainto a mold to form a syringe.

FIG. 1C illustrates a side, cross-sectional view of the syringe of FIG.1B.

FIG. 1D illustrates a cross-sectional enlargement of the rearward end ofthe syringe of FIG. 1C.

FIG. 1E illustrates a cross-sectional enlargement of the forward end ofthe syringe of FIG. 1C.

FIG. 1F illustrates a perspective view of the syringe of FIG. 1C.

FIG. 1G illustrates a front view of the syringe of FIG. 1C.

FIG. 2A illustrates another embodiment of a preform of the presentdisclosure.

FIG. 2B illustrates the stretch blow molding syringe formed from thepreform of FIG. 2A with the stretch rod therein.

FIG. 2C illustrates an enlargement of the rearward end of the syringe ofFIG. 2B.

FIG. 2D illustrates a side view of the stretch rod.

FIG. 2E illustrates a side cross-sectional view of the syringe of FIG.2B.

FIG. 2F illustrates a cross-sectional enlargement of the syringe of FIG.2B.

FIG. 2G illustrates the stretch blow molding syringe of FIG. 2A withinthe mold therefor.

FIG. 2H illustrates the syringe of FIG. 2B in operative connection withan injector.

FIG. 2I illustrates a blow molded fluid path element of the presentdisclosure including a precision molded Luer connection in the vicinityof one of two openings thereof and a precision molded threadingconnection in the vicinity of the other of the two openings.

FIG. 2J illustrates a blow molded manually operated syringe of thepresent disclosure.

FIG. 3A illustrates another embodiment of a syringe of the presentdisclosure including an integral syringe tip closure.

FIG. 3B illustrates an enlarged view of the syringe tip of the syringeof FIG. 3A.

FIG. 4A illustrates another embodiment of a syringe of the presentdisclosure including an integral rearward closure.

FIG. 4B illustrates an enlarged view of the rearward section of thesyringe of FIG. 4A.

DETAILED DESCRIPTION

In general, the present disclosure provides hollow article devices suchas syringes and methods of manufacture of such devices using blowmolding processes. The present disclosure is discussed below primarilywith reference to representative embodiments of syringes for injectionof a fluid into a patient. However, one skilled in the art appreciatesthat the methods of the present disclosure can be used to form a numberof hollow article devices (including, for example, medical flow pathelements or devices).

Blow molding is a method of forming hollow articles from polymeric(thermoplastic) materials. Simplifying, the blow molding processinvolves forming a heated tube within a mold cavity using a pressurizedgas (typically, compressed air). The three most common methods of blowmolding are extrusion blow molding, injection blow molding andinjection-stretch blow molding. In extrusion blow molding, tubes orparisons are extruded into alternating open mold halves and then blownand cooled prior to removal from the mold. In injection blow molding, a“preform” component is first injection molded. The preform is then blownto the product's final shape. Injection blow molding can providedimensional precision in certain critical areas. The injection blowmolding process can be performed using separate machines or through useof shuttling or rotating molds. In the injection-stretch blow moldingprocess, a preform is, once again, first injection molded. Duringsubsequent blowing, however, the preform/parison is mechanicallyextended at an optimal temperature, while radially blown to shape withinthe mold. Injection-stretch blow molding provides a biaxial stretch toenhance material properties. For example, the biaxial orientation canincrease tensile strength by an order of five or more. Furthermore,biaxial orientation can enhance other material properties, such asclarity, barrier properties (2× or more), and mechanical properties. Forexample, crystallinity of certain polymers can be controlled. In severalembodiments for syringes of the present disclosure manufactured from,for example, polyethyleneterephthalate, crystallinity can be increasedto as high as approximately 43% (for example, via mechanical and/orthermal processing) to maximize these improvements. One skilled in theart also realizes that further increasing crystallinity can bedetrimental and decrease optical properties and cause the material to betoo brittle.

The present inventors have discovered that the improved mechanicalproperties provided by blow molding of, for example, syringes can enablea decrease in the barrel wall thickness of a syringe as compared to aninjection molded syringe while maintaining an acceptable safety factorover a range of operating pressures. Moreover, use of a blow moldingprocess in the manufacture of syringes and other devices cansubstantially increase manufacturing throughput. Indeed, significantreduction in manufacturing cost can result from using a blow moldingprocess to manufacture syringes for use with powered injectors andnon-powered or manually powered syringes. Likewise, significantreduction in manufacturing cost can result from using a blow moldingprocess to manufacture other devices including, but not limited to,hollow devices used in flow paths for medical fluids.

FIGS. 1A through 1G illustrate one embodiment of a preform 10 and a blowmolded, closed-ended syringe 10′ that was used in several studies of thepresent disclosure. Preform 10 was first molded using an injectionmolding process. The injection molding process facilitates the formationof areas wherein dimensions are critical (that is, areas in whichcertain dimensional tolerances must be maintained), such as the injectoror other attachment mechanism 20 on the rearward end of preform 10. Inthe embodiment of FIGS. 1A through 1G, injector attachment mechanism 20includes a flange 22 that extends around the circumference of preform 10and syringe 10′. Preform 10 and syringe 10′ also include a drip flange30 that cooperates with a front wall of an injector (not shown) to, forexample, assist in accurately positioning syringe 10′ within theinjector and to prevent fluids from entering the injector housing.Injector attachment or mounting flange 22 and drip flange 30 remainessentially unchanged from preform 10 to blow molded syringe 10′.Syringes including such an injector attachment design and injectors foruse therewith are described, for example, in U.S. Pat. Nos. 5,383,858and 6,665,489, the disclosures of which are incorporated herein byreference. As further discussed below, one skilled in the artappreciates that syringes having virtually any type of attachmentmechanism and/or one or more other precision molded, elements portionsor sections can be manufactured using the methods and systems of thepresent disclosure.

FIG. 1B illustrates preform 10 within a mold 100 in which it undergoesstretch blow molding to result in syringe 10′. In FIG. 1B, preform 10 isillustrated in thickened lines for clarity. Likewise, barrel 12′ ofsyringe 10′ is illustrated in thickened dashed lines for clarity. Barrel12′ included a forward closed end 14′ in this embodiment. Mountingflange 22 and drip flange 30 cooperated with corresponding retainingflanges in mold 100 to retain the rearward end of preform 10 and syringe10′ throughout the stretch blow molding process. Once again, mountingflange 22 and drip flange 30 (and/or other molded elements which aremolded to have certain dimensions and associated tolerances) remainessentially unchanged during the stretch blow molding process. In thatregard, it may be desirable to maintain the preheat temperature in therearward portion of preform 10 and syringe 10′ relatively cool (belowthe T_(g) of the material) as compared to the remainder of the mold toprevent deformation of mounting flange 22 and drip flange 30 (and/orother elements) during the blowing process. Heat shielding can also beused. In general, those sections of mold 100 forward of drip flange 30are preheated in a preheating unit to a temperature sufficiently high tomaintain the temperature of the preform/syringe above the glasstransition (T_(g)) of the thermoplastic during the molding process.After preheating, preform 10 is placed into mold 100. In several studiesof the present disclosure, there was no further heating in mold 100. Ina number of studies of the present disclosure, polyethyleneterephthalate(PET) or cyclic olefin polymer (COP) was used. The COP used was ZEONOR®1410R available from Zeon Chemicals LP of Louisville, Ky. COP is, forexample, suitable for sterilization (for example, high energysterilization (such as radiation), chemical sterilization (such asethylene oxide), autoclave sterilization and/or steam sterilization) andcan, for example, be used in connection with prefillable syringes. Asclear to one skilled in the art, a variety of polymeric materials can beused in the devices, systems and methods of the present disclosure. Ingeneral, materials that can undergo orientation (for example, biaxialorientation) during the molding process can be preferred in certain usesbecause of the enhanced properties exhibited by such materials. Inaddition to PET and COP, such materials include, but are not limited to,polypropylene, polystyrene and polyvinylidene chloride (PVDC).

As described above, during the stretch blow molding process, stretch rod320 is extended forward, while compressed air is blown into the interiorof preform 10 until preform 10 is expanded to fill the mold cavity,thereby forming syringe 10′ including barrel 12′ in which thethermoplastic is biaxially oriented (that is, oriented axially or in thedirection of axis A and radially/tangentially or in a direction normalor around to axis) as described above. In this embodiment, stretch rod320 pushes against closed end 14′ during the blow stretch moldingprocess. Upon cooling, syringe 10′ is removed from mold 100.

To achieve high pressures, smooth plunger movement within the syringe,limit blow by, and/or provide predictable volume in the syringes of thepresent disclosure, it is desirable to have an inner diameter in thesyringe barrel having a relatively consistent wall thickness. To ensurea relatively consistent wall thickness and therefore a predictable,relatively consistent interior syringe barrel diameter with adequatestrength, the preform design is important. For example, the area infront of the drip flange 30 may undergo a stretch of up to four (4)times its original length and width in preform 10 to meet the finaldimensions in syringe 10′. If the material stretches unevenly as aresult of design or heating limitations, such stretching variabilitymust be provided for in the preform design. For example, additionalmaterial may be required in areas of high stretch. On the other hand,reduced material may be required in areas of low stretch. Alternativelyor additionally, the rate or speed of stretch, the preform temperature,and blow pressure can be varied. The inventors of the present disclosurehave discovered that relatively consistent and predictable wallthickness and internal diameter can be readily achieved in blow moldedsyringes. The process considerations set forth above are known to thoseskilled in the blow molding arts and can result in a syringe barrelcompatible with high-pressure (for example, 50 psi to 1500 psi) use andadequate/predictable fluid performance. An example of an acceptabledelivery volume tolerance in an injection system is approximately ±2%+1mL. In meeting a suitable delivery volume tolerance, the inner diametersof the syringes of the present disclosure preferably do not vary bygreater than 0.01 inches. Variances of no greater than 0.007 inches ininner diameter are also achievable. Indeed, variances of no greater than0.004 inches in inner diameter are also achievable over the pressurizingzone of the syringe.

In several studies of the syringes of FIGS. 1A through 1B, 60 blowmolded syringes were used and divided into 3 lots of differing PETfabrication material of 20 syringes each. Preferably, the PET materialexhibited partial crystallinity after blow molding. The three PETmaterials used to fabricate the syringes EN001 PET, EN063 PET and HWCF746 PET, available Eastman Chemical of Kingsport, Tenn. The syringestested had a wall thickness of approximately 0.030 in. In pressuretesting the syringe, triple seal RTF plunger as described, for example,in U.S. Pat. Nos. 5,873,861, 6,017,330 and 6,984,222, the disclosures ofwhich are incorporated herein by reference. Many other plungers,including other dynamically sealing plungers as, for example, describedin U.S. Pat. No. 6,224,577, the disclosure of which is incorporatedherein by reference, can also be used effectively in the syringes of thepresent disclosure. A universal tensile testing machine available fromInstron of Norwood, Mass. was used in the testing. Samples for tensilestrength testing were cut for testing using a die as known in the art.Several properties of the PET materials studied in the presentdisclosure are set forth below in Table 1 as determined using the testconditions and procedures of ASTM D 638, the disclosure of which isincorporated herein by reference. In the case that PET polymers orcopolymers are used, such polymer can, for example, have an intrinsicviscosity in the range of 0.65 to 1.04 dl/g (deciliters/gram). As knownin the art, intrinsic viscosity is dependent upon the length of thepolymer chains of the polymer.

TABLE 1 EN001 EN063 HW CF746 Stress @ yield (psi) 8,400 8,400 notavailable Stress @ break (psi) 3,600 4,600 not available Modulus (psi)350,000 360,000 not available

Static high pressure testing was performed at 2 mL/s for 5 samples fromeach lot using water. In the static high pressure test, each syringe wasfilled to just below drip flange (approximately 75% full). The plungerwas then installed. The syringe was retained in a holding fixture in theInstron universal tensile testing machine while a measurable force wasapplied to plunger. The Instron universal tensile testing machine, whichwas calibrated for flow rate, was set at 2 ml/sec and failure mode wasrecorded. Three PET material types, as described above, were tested. Thestatic high pressure testing resulted in an average pressure of 342 psiwith a standard deviation of 40 psi for EN001 PET. Failure modes werebarrel burst and blow by. The static high pressure testing resulted inan average pressure of 310 psi with a standard deviation of 171 psi forEN063 PET. Potential failure modes were barrel burst and blow by. Thestatic high pressure testing resulted in an average pressure of 305 psiwith a standard deviation of 67 psi for HW CF746 PET. The failure modewas barrel burst.

Dynamic pressure testing was performed at 5 ml/s for 5 samples from eachlot using saline. Dynamic pressure and capacitance testing wereperformed only for EN001 PET as the force to fail was the largest forthat material of the three material types tested. In these tests, closedend 14′ of syringes 10′ was drilled out and a metal luer connection wasconnected. A flow restrictor valve was connected to the luer connection.The Instron was set at 5 ml/sec. The flow restrictor valve was adjustedto generate a pressure of 100 psi. The average dynamic friction forcewas 50 lbs or 18.7 psi at a syringe pressure of 100 psi.

In tensile strength testing, samples were first cut out using thetensile bar cutting die. Tests were then performed in accordance withthe testing procedures set forth in ASTM D638. Samples were cut radially(5 samples of each lot) as well as axially (5 samples of each lot). FIG.1E illustrates generally how axial and radial samples were cut fromsyringes 10′. The results of several tensile strength studies are setforth in Table 2.

TABLE 2 Maximum Stress @ Stress @ Stress Break Yield Modulus Strain @Strain @ (psi) (psi) (psi) (psi) Break Yield 001 Axially 16546 1621610842 475964 52 3 001 Radially 9146 5095 8914 344345 31 4 063 Axially13990 9632 11146 485791 39 3 063 Radially 9214 1594 9196 353298 25 4 HWAxially 12024 7670 10409 527765 29 3 HW Radially 8440 4360 7642 52741318 3

In several capacitance testing studies of the syringes of the presentdisclosure, a metal luer was installed in syringes 10′ as describedabove, and syringes 10′ were filled with water. A rubber O-ring plungerwas inserted and the plunger was advanced until the front of the plungerwas approximately 1 inch past drip flange 30. Syringe 10′ was thenmounted onto the Instron. The Instron was set to run at 2 in/min and tostop at a load of 540 lbs. A 3-way stopcock was installed on the end ofthe syringe, and a scale was placed under the syringe with a beaker tocapture the fluid. A piece of connector tubing was attached to the metalluer fitting that was of sufficient length to reach into the beaker.Care was taken so that the tubing did not come in contact with thebeaker. The Instron was then run. When the 540 lb limit was reached, thestopcock was turned slowly to dispense the fluid into the beaker.Subsequently, the stopcock was returned to the closed position todispense the remaining fluid out of the line. The volume of fluiddispensed into the beaker was recorded. The results of several studiesare set forth in Table 3.

TABLE 3 Syringe # Fluid Dispensed 73 6.3 ml 94 6.6 ml 74 4.8 ml 71 6.3ml

In general, neither the tested syringes nor the method of manufacturewas optimized in the above studies. The failure mode observed during theburst pressure tests, were almost all a result of splitting at the blowmold parting line. The blow mold parting line is the split between themold halves. A non-optimized parting line can cause undue materialstress and malformation, which may weaken this area. Optimizing theparting line (which was not done in the present studies) can, forexample, be accomplished by ensuring a minimal mismatch and sharp cleanedges on the parting line of the blow molding tool. The friction forceand static pressure were found to be relatively consistent in the testedsyringe with the highest level of consistency realized with the EN001material. The data suggested that the blow-up ratio to tensile strengthis a linear function, which correlates with published information oninjection-stretch blow molding. These results reflect a 2 to 1 ratio onthe axial dimension and a 1 to 1+ on radial dimensions. The EN001material exhibited the highest increase. The friction force was found toconsistent along the length of the barrel. Moreover, the barrel wallthickness was consistent, as interpolated from the friction data.

A “heat setting” process as known in the blow molding arts (effected,for example, via heating the blow mold cavities to elevatedtemperatures) may be desirable, for example, in the case that ethyleneoxide (EtO) sterilization is to be used, as a result of the elevatedtemperatures used during EtO sterilization. The elevated temperatures ofthe EtO sterilization process may cause the suitable or acceptabledimension of the syringe barrel internal diameter to relax or change toan unacceptable dimension. The syringe plunger, which is sealingly andslidably positioned within the syringe barrel, exerts an outward forceto ensure an adequate seal against the barrel wall to prevent leakagewhen pressurized during use. The heat setting process prevents thebarrel wall from expanding or contracting and changing to anunacceptable dimension. It is not believed that a “heat setting” processwill be required to control or improve the fluid capacitance of thesyringe barrel. However, the results indicate that syringe fluidcapacitance can also be improved with blow molding (for example, viaheat setting), as compared to injection molding even with a relativelythin wall. The wall thickness of the syringes studied in the presentdisclosure was approximately 0.030 inches (versus, for example,approximately 0.79 for a typical injection molded syringe). The pressurecapability of the syringe barrel can, for example, be improved by usinga preform which exhibits a higher stretch ratio with the same wallthickness. The preform design can also be improved or optimized to, forexample, take advantage of the PET “self-leveling” materialcharacteristics, which will improve dimensional consistency and increaseoverall material strength. In general, self-leveling is the ability forthe polymer to stretch, such that it pulls from a thicker cross sectioninstead of a thinner cross section. If the cross section is properlysized to the total expansion, the final component will exhibit aconsistent wall thickness.

FIGS. 2A through 2H illustrate another embodiment of a preform 210 and ablow molded, open-ended syringe 210′. As with preform 10, preform 210 isfirst molded using an injection molding process. The injection moldedprocess facilitates the formation of areas in which dimensionaltolerances are critical such as the injector attachment mechanism 220 onthe rearward end of preform 210. In the embodiment of FIGS. 2A through2H, injector attachment mechanism 220 includes a flange 222 that extendsaround the circumference of preform 210 and syringe 210′. In theillustrated embodiment, preform 210 and syringe 210′ also include a dripflange 230. Syringe 210′ can alternatively or additionally include otherprecision molded portions or sections. Once again, injector attachmentor mounting flange 222 and drip flange 230 (and/or other precisionmolded portions) remain essentially unchanged from preform 210 to blowmolded syringe 210′. A stretch rod 320 can be incorporated into theblowing mold process to induce biaxial orientation and to assist in, forexample, ensuring that premolded features forward of the portion ofpreform 210 to be expanded such as illustrated in FIG. 2F and discussedfurther below are not harmed (for example, that the dimensions thereofare not substantially altered and required tolerances are maintained)during the blowing molding process. After the preform 210 is preheatedas described above and placed into the blowing mold, two halves 305 ofthe blowing mold (see FIG. 2G) are closed. When properly clamped,stretch rod 320 is moved linearly to engage tip 330 into the internalaspect of syringe tip 214. Stretch rod 320 continues to move forwardforcing syringe tip 214 into a protected mold area shaped in the form ofsyringe tip 214 and/or other forward precision molded component (seeFIG. 2G). This area of the mold as well as the area encompassingmounting flange 222 and drip flange 230 can be maintained below moldingtemperature, so that the dimensions of the premolded syringe tip 214,the premolded mounting flange, and the premolded drip flange 230 are notaffected/altered.

Similar to preform 10, preform 210 is placed within the mold, asillustrated in FIG. 2G, in which it undergoes stretch blow molding toresult in syringe 210′. Preform 210 and syringe 210′ included forward,open-ended syringe tip 214 including a syringe outlet 214 a having anintegrally or monolithically formed, precision molded connector such asa connector including a male luer taper and a luer threading 214 b inthe illustrated embodiment. Barrel 212′ is connected to syringe tip 214by a rounded (in cross section) transition region 216′. Mounting flange222 and drip flange 230 cooperate with corresponding retaining flangesin the mold to retain the rearward end of preform 210 and syringe 210′throughout the stretch blow molding process.

As described above, during the stretch blow molding process, stretch rod320 is extended forward, while compressed air is blown into the interiorof preform 210 until preform 210 is expanded to fill the mold cavity,thereby manufacturing syringe 210′ including barrel 212′ in which thethermoplastic is biaxially oriented. In this embodiment, stretch rod 320includes a forward section 330 dimensioned to enter and at leastpartially seal the rearward portion of syringe tip 214′ (from fluidconnection with the portion or preform 210 being expanded), therebyassisting in maintaining pressure within expanding barrel 212′. Stretchrod 320 also pushes against syringe tip 214′ during the blow stretchmolding process as described above to, for example, assist in achievingbiaxial orientation. Moreover, stretch rod 320 at least partiallyprevents heated gas from entering syringe tip 214, (which is injectionmolded during fabrication of preform 210 to predefined acceptabletolerances), thereby assisting in maintaining syringe tip 214essentially unaltered during the blow molding process.

FIG. 2H illustrates syringe 210′ in operative connection with aninjector including a controller and a motor in operative connection withthe controller to control the powered motion of a drive member or piston350 in operative connection with syringe plunger 250 which is slidablypositioned within syringe barrel 212′. As described above, injectorssuitable for use with various syringes of the present disclosure aredisclosed, for example, in U.S. Pat. No. 5,383,858 and U.S. Pat. No.6,652,489.

FIG. 2H also illustrates that the wall of syringe 210′ can include afirst layer 212 a′ of a first polymeric material and at least a secondlayer 212 b′ of a second polymeric material, different from the firstpolymeric material. At least one of the first polymeric materials can,for example, include polyethyleneterephthalate, cyclic olefin polymer,polypropylene, polystyrene, polyvinylidene chloride, polyethylenenaphthalate and/or nylon. The second polymeric material can, forexample, be nylon, ethylene vinyl alcohol copolymer (EVOH),polycarbonate or other suitable polymers as known in the art. EVOH, forexample, provides good barrier properties and may be used in connection,for example, with prefillable syringes. The first and/or the secondpolymeric material can, for example, include a single polymer or blendsof two or more polymers. The polymeric materials of the first layer andthe second layer can, for example, differ in one or more respects suchas composition, molecular weight, crystallinity, barrier properties etc.As known in the blow molding arts, an adhesive or tie layer 212 c′ canbe used between polymeric layers to strengthen the bond between suchlayers. Suitable adhesives or tie layers include those known in the artthat are useful in adhering layers of dissimilar polymeric materials andin achieving an improved interlayer bond strength. An example of asuitable adhesive or tie layer material is ADMER® (a modified polyolefinwith functional groups available from Mitsui Chemicals America, Inc. ofRye Brook, N.Y.) that is suitable to bond to a variety of polymersincluding, for example, polyolefins, ionomers, polyamides, ethylenevinyl alcohol (EVOH), PET, polycarbonates, and polystyrenes.

In general, the process described above in connection with the syringeof FIGS. 2A through 2H can be used to create any hollow device orapparatus that is open at both ends via a blow stretch molding process.The process is thus well suited for fabricating many fluid flow pathelements used, for example, in the medical arts. As used herein, theterm “flow path element” refers generally to any device or elementthrough which a fluid (for example, a liquid and/or gas) flows (forexample, in a medical system). Such flow path elements are open at eachend and at least one end thereof, and often each ends thereof, includesan attachment mechanism and/or or other portion or section molded tocertain predefined acceptable tolerances to, for example, enablingattachment of the flow path element to other devices and/or flow pathelements. As known in the art, connector or attachment mechanisms cantake a wide variety of forms (for example, threaded attachments, snapattachments, friction attachments, Luer attachments, plug fits etc.). Asalso known in the art, it is desirable to mold such connector orattachment mechanism or mechanisms within specific tolerances to, forexample, ensure a non-leaking, high-pressure seal. As described above,the blow stretch molding processes and systems of the present disclosureare well suited to expand the intermediate portion or section of thedevice or flow path element while the dimensions and other properties ofthe precision molded portions on one or both ends of the device areessentially unaltered. In that regard, the blow stretch molding methodsand systems of the present disclosure are suited to maintain commonproduction tolerances (both fine and commercial standards) for a widevariety of polymeric materials as described, for example, in Whitmore,E. M., editor, Standards & Practices of Plastics Molders—Guidelines forMolders and Their Customers, Molders Division, Sponsored by the Societyof the Plastics Industry, Inc. (1993). The blow stretch molding methodsand systems of the present disclosure are, for example, suitable tomaintain tolerances of end attachments or other molded features to plusor minus 0.05, 0.02, 0.01, 0.005 and even 0.002 for a variety ofpolymeric materials.

FIGS. 2I and 2J illustrate examples of fully formed flow path elementsand devices that can be fabricated using the blow stretch moldingmethods of the present disclosure. FIG. 2I illustrates a flow pathelement 360 (for example, a drip chamber) having an inlet 362 and anoutlet 364. Each of inlet 362 and outlet 364 are injection molded toincorporated precision molded connection or attachment mechanisms beforethe blow stretch molding process. In that regard, inlet 362 includes athreaded connection in the vicinity thereof, and outlet 364 includes amale Luer connection in the vicinity thereof. The dimensions/tolerancesof the precision molded connection mechanisms (and/or other precisionmolded components) are essentially unaltered during the expansion ofintermediate (hollow) section 366 during the blow stretch moldingprocess.

FIG. 2I illustrates an embodiment of a low-pressure, manually operatedsyringe 370 formed by a blow stretch molding process of the presentdisclosure. Syringe 370 includes a rearward or proximal opening 372 anda forward or distal outlet 374 in the form of a male Luer fitting. Amanually operated plunger extension 380 connects to syringe plunger 382slidable positioned within syringe barrel 376 through rearward opening372. Syringe 370 further includes finger grips 378. Thedimensions/tolerances of the Luer connector finger grips 378 areessentially unaltered during the expansion of syringe 376 during theblow stretch molding process.

FIGS. 3A and 3B illustrate another embodiment of a syringe 410′ of thepresent disclosure which is blow molded from a preform (not shown). Inthis embodiment, syringe 410′ includes a rear mounting flange 422 and aforward syringe tip 414 that remain essentially unchanged during theblow molding process. As described above, barrel 412′ and transitionregion 416′ are expanded to fill the mold cavity during the blow moldingprocess.

In this embodiment, syringe tip 414 includes an integrally moldedsyringe tip closure 418 that is molded integrally with syringe tip 414during the injection molding of the preform. Syringe tip closure 418can, for example, be connected to syringe outlet 414 a via an area ofreduced wall thickness 419 so that syringe tip closure 418 can bereadily broken off to open syringe outlet 414 a. Syringe tip closure 418can, for example, assist in maintaining sterility in the case of aprefilled syringe. The integrally molded syringe tip closures of thepresent disclosure can also be provided on syringes that are not blowmolded (for example, injection molded syringes).

FIGS. 4A and 4B illustrate another embodiment of a syringe 510′ of thepresent disclosure blow molded from a preform (not shown). In thisembodiment, syringe 510′ includes a rear mounting flange 522 and aforward syringe tip 514 that remain essentially unchanged during theblow molding process. As described above, barrel 512′ and transitionregion 516′ are expanded to fill the mold cavity during the blow moldingprocess. In the embodiment of FIGS. 4A through 4B, compressed air can,for example, be blown into the preform through syringe tip 514 a tocreate the rearward, integral or monolithic closure/plunger cover 540 ina blow molding process. Extrusion blow molding can, for example, be usedin this embodiment.

With reference to FIG. 4B, in several embodiments, closure 540 isremovable at edges 542 thereof (for example, via areas of reduced wallthickness, channels, notches etc.) from the connection with theremainder of syringe 512′. As described above, the removable closurecan, for example, form a plunger section upon removal from connectionwith the remainder of syringe 512′. Plunger or plunger cover 540 forms asubstantially sealing engagement with the inner wall of syringe 512′when slid through the barrel thereof. In the illustrated embodiment,plunger 540 includes a flange 544 attached at a rearward portion offlange 544 to body or central portion 548 of the plunger 540. Flange 544extends forward and radially outward to form a circumferential channel546 between flange 544 and body 548 of plunger 540. During use ofsyringe 512′, fluid within syringe 512′ enters annular channel 546.Forward motion of plunger 540 to pressurize and inject fluid containedwithin syringe 512 results in pressurization of the fluid within annularchannel 546. The hydraulic force of the fluid within annular channel 546forces flange 544 away from body portion 548 and against an inner wallof syringe 512′. As plunger 540 is moved forward, flange 544 is forcedagainst the inner wall of syringe 512′ and prevents any fluid frompassing rearward between flange 544 and the inner wall of syringe 512′.The operation of plungers including such a “wiper seal” is discussed,for example, in U.S. Pat. No. 6,224,577.

Although the present disclosure has been described in detail inconnection with the above embodiments and/or examples, it should beunderstood that such detail is illustrative and not restrictive, andthat those skilled in the art can make variations without departing fromthe disclosure. The scope of the disclosure is indicated by thefollowing claims rather than by the foregoing description. All changesand variations that come within the meaning and range of equivalency ofthe claims are to be embraced within their scope.

What is claimed is:
 1. A preform for a stretch blow molded syringe, thepreform comprising: a proximal end having a retention mechanism, theretention mechanism adapted to connect the syringe to a poweredinjector; a distal end having a syringe outlet section; and a barrelsection between the retention mechanism and the syringe outlet section,wherein the preform comprises at least one polymeric material, andwherein the barrel section is adapted to be stretch blow molded to forma cylindrical wall of a syringe barrel defined between the retentionmechanism and the syringe outlet section, and wherein the syringe outletsection in formed during an injection molding process of the preform andis not substantially altered during a stretch blow molding expansionprocess.
 2. The preform of claim 1, wherein the retention mechanism isformed during an injection molding process of the preform.
 3. Thepreform of claim 2, wherein the retention mechanism is not substantiallyaltered during the stretch blow molding expansion process.
 4. Thepreform of claim 1, wherein the syringe outlet section comprises aconnector adapted to connect with a complementary connector of a fluidpath element.
 5. The preform of claim 4, wherein the connector is one ofa male luer connector or a female luer connector.
 6. The preform ofclaim 4, wherein the connector comprises an outlet passage.
 7. Thepreform of claim 1, wherein the at least one polymeric material of thepreform comprises at least one of polyethylene terephthalate, cyclicolefin polymer, polypropylene, polystyrene, polyvinylidene chloride,polyethylene naphthalate, or nylon.
 8. The preform of claim 1, whereinthe preform comprises a first layer of a first polymeric material and atleast a second layer of a second polymeric material, wherein the secondpolymeric material is different from the first polymeric material. 9.The preform of claim 1, further comprising a transition region betweenthe barrel section and the syringe outlet section of the preform,wherein the transition region forms a conical section between thecylindrical side wall and the syringe outlet section of the stretch blowmolded syringe.
 10. The preform of claim 1, wherein the barrel sectionis adapted to be stretch blow molded to form the cylindrical wall of thesyringe barrel, wherein the cylindrical wall has an inner diameter thatis substantially constant.
 11. The preform of claim 10, wherein theinner diameter of the cylindrical wall does not vary by greater than0.01 inches.
 12. The preform of claim 10, wherein the cylindrical wallof the syringe barrel is less than 0.07 inches in thickness.
 13. Thepreform of claim 1, wherein the preform is adapted to be biaxiallystretched during stretch blow molding.
 14. A preform for a stretch blowmolded syringe, the preform comprising: a proximal end having aretention mechanism; a distal end having a syringe outlet section; and abarrel section between the retention mechanism and the syringe outletsection, wherein the barrel section is adapted to be stretch blow moldedto form a cylindrical wall of a syringe barrel defined between theretention mechanism and the syringe outlet section, wherein theretention mechanism remains on the syringe after stretch blow moldingand is adapted to connect the syringe to a connection mechanism of apowered injector.
 15. The preform of claim 14, wherein the barrelsection is adapted to be stretch blow molded by biaxial stretching. 16.A method for stretch blow molding a preform to produce a stretch blowmolded syringe, the method comprising: providing an injection moldedpreform comprising: a proximal end having a retention mechanism formedduring an injection molding process of the preform, the retentionmechanism adapted to connect the syringe to a powered injector; a distalend having a syringe outlet section formed during the injection moldingprocess of the preform; and a barrel section between the retentionmechanism and the syringe outlet section; and stretch blow molding thepreform to provide a stretch blow molded syringe having a biaxiallystretched cylindrical side wall between a syringe proximal endcomprising the syringe retention mechanism and a syringe distal endcomprising the syringe outlet section, wherein the syringe outletsection and the retention mechanism are not substantially altered duringthe stretch blow molding step.
 17. The method of claim 16, whereinstretch blow molding the preform comprises blowing compressed air intothe preform through the syringe outlet section.
 18. The method of claim16, wherein the stretch blow molded syringe comprises a rearward,monolithic closure.
 19. The method of claim 16, wherein the injectionmolded preform further comprises a transition region between the barrelsection and the syringe outlet section, wherein the transition regionforms a conical section between the cylindrical side wall and thesyringe outlet section of the stretch blow molded syringe.